The goal of this proposal is to perform first-in-man evaluation of the imaging probe [18F]BF4 as a PET imaging biomarker for expression of the human sodium/iodide symporter (hNIS) in tissues. Imaging of functional hNIS activity in tissues with [18F]BF4 is anticipated to provide superior sensitivity and image quality to 123I or 99mTc SPECT for monitoring hNIS transduction effected by gene therapies. Furthermore, imaging of hNIS activity may help evaluation of thyroid cancers, an application not explored in this proposal. The proposed work is designed to 1) develop an automated synthesis of high-specific activity [18F]BF4, 2) evaluate its safety, biodistribution, metabolism and radiation dosimetry characteristics in 8 healthy human volunteers and 3) evaluate the imaging feasibility of hNIS expression in a) 10 cancer patients treated with Edmonston Measles virus-NIS (MV-NIS) and b) 10 endometrial cancer patients treated with vesicular stomatitis virus engineered to express human interferon-? and NIS (VSV-hINF?-NIS) in comparison with Tc-99m SPECT imaging. This data will be necessary to support future regulatory submissions. The specific aims of the proposal are: Aim 1. Based on excellent preliminary results with a high-specific activity synthesis of [18F]BF4 via radiofluorination of boron trifluoride, we will develop an automated synthesis module and process for preparation of [18F]BF4. Conditions will be optimized for radiochemical yield, radiochemical purity, and specific activity. Aim 2. Define the safety, biodistribution, metabolism, and radiation dosimetry characteristics for [18F]BF4 in human subjects. Dynamic whole-body [18F]BF4-PET imaging will be performed in 8 normal adult human subjects (4 male, 4 female) over a 4 h period. IV blood samples will be taken and analyzed to determine radiochemical stability. Radiation dosimetry estimates will be generated from the regional uptake data. Aim 3. Perform [18F]BF4-PET and [99mTc]pertechnetate-SPECT imaging in 10 patients with myeloma before MV-NIS treatment, and at Day 8 to monitor NIS activity in the tumors. To show the correlation of positive regional uptake with tissue histopathology for NIS, biopsies will be taken, when accessible, after the day 8 scan. Aim 4. Perform [18F]BF4-PET and [99mTc]pertechnetate-SPECT imaging in 10 patients with endometrial cancer before VSV-hINF?-NIS treatment, and at Day 8 to monitor NIS activity in the tumors. To show the correlation of positive regional uptake with tissue histopathology for NIS, biopsies will be taken, when accessible, after the day 8 scan.